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Pakistan Journal of Pharmaceutical... Jul 2022Meloxicam (MEL) is an oxicam derivative with low water solubility that is useful in the treatment of colorectal cancer (CRC) as a COX-2 inhibitor. MEL-loaded HPMC micro...
Meloxicam (MEL) is an oxicam derivative with low water solubility that is useful in the treatment of colorectal cancer (CRC) as a COX-2 inhibitor. MEL-loaded HPMC micro particles were fabricated using an oil-in-oil (o/o) emulsion solvent evaporation (ESE) method. FTIR, XRD, particle size analysis, DSC, SEM and in vitro dissolution investigation were utilized to evaluate the produced micro particles physiochemically. Finally, rabbits were used as animal models in an in vivo pharmacokinetic study to assess the MEL concentration in the plasma of rabbits. Pure MEL, F1 and F2 were given to rabbits by a single dose for in vivo pharmacokinetic investigations. The XRD and DSC results confirmed the transformation of MEL from its crystalline nature to the amorphous state in micro particles. The formulations F1 and F2 particle sizes were determined 92.43μm and 163.26μm, respectively. The prepared micro particles had a smooth, non-porous and spherical surface. In comparison to the pure drug (22.4%), the F1 and F2 cumulative drug release (%) was 86.19% and 79.57%, respectively. Pure MEL, F1 and F2 have estimated C values of 7.21, 25.41 and 22.38μg/mL, respectively. MEL had a half-life of 19.98 hours, which rose to 22.19 hours and 24.75 hours for F1 and F2, respectively. MEL, F1 and F2 had AUC0-α values of 116.034, 445.95 and 462.72μg/mL*h, respectively. Considering these aspects, MEL-loaded HPMC micro particles may have the potential to better the delivery and control the release of drug that is not easily dissolved in water which could lead to improved therapeutic efficacy and limited side effects.
Topics: Animals; Cyclooxygenase 2 Inhibitors; Emulsions; Hypromellose Derivatives; Meloxicam; Methylcellulose; Particle Size; Rabbits; Solubility; Solvents; Water
PubMed: 36218104
DOI: No ID Found -
Biomedical Chromatography : BMC Aug 2022A rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to detect meloxicam in human...
A rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to detect meloxicam in human plasma. A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source was used in positive ion mode. Protein precipitation with acetonitrile was used for sample preparation. Meloxicam and C -meloxicam internal standard were analyzed on an Acquity CSH C column with a mobile phase of acetonitrile and water in 0.1% formic acid using a gradient program for separation. The retention time of meloxicam was 1.1 min and the total run time was only 2.0 min. Detection was performed in multiple reaction monitoring mode using an electrospray ionization source with optimized mass spectrometry parameters. The calibration curves were linear in the range 10.0-3.00 × 10 ng/ml (r ≥ 0.99). The within-run and between-run RSDs were ≤14.8%. The within-run and between-run REs ranged from -4.6 to 10.7%. There was no significant matrix effect, and the recovery rate was high. This method was fully validated, including reinjection reproducibility in human plasma. The method was applied to the pharmacokinetic study. All of the incurred sample reanalysis methods met the criteria.
Topics: Acetonitriles; Chromatography, High Pressure Liquid; Humans; Meloxicam; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 35514216
DOI: 10.1002/bmc.5395 -
Journal of Equine Veterinary Science Feb 2023Flunixin meglumine (FM), a nonselective cyclooxygenase (COX) inhibitor, is most frequently selected for the treatment of equine systemic inflammatory response syndrome...
Flunixin meglumine (FM), a nonselective cyclooxygenase (COX) inhibitor, is most frequently selected for the treatment of equine systemic inflammatory response syndrome (SIRS)/endotoxemia. However, FM has considerable adverse effects on gastrointestinal function. The aims of this study were to compare the effect of meloxicam (MX), a COX-2 selective inhibitor commonly used in equine clinical practice, with FM, and to investigate the potential for clinical application in horses with SIRS/endotoxemia. Fifteen horses were divided into three groups of five and orally administered MX (0.6 mg/kg), FM (1.1 mg/kg), or saline as placebo at 30 minutes after LPS challenge. Clinical parameters, including behavioral pain scores, were recorded and blood for clinical pathological data was collected at various times from 60 minutes before to 420 minutes after LPS infusion. The pain score were significantly lower in both the MX and FM groups than in the placebo group, with no significant difference between them. Body temperature was significantly lower in the MX and FM groups than in the placebo group. Heart rates and respiratory rates, hoof wall surface temperature, and leukocyte counts changed similarly between the MX and FM groups. TNF-α and cortisol were lower in the FM group than in the MX group. The results suggest that MX suppresses the inflammatory response after LPS infusion and has an analgesic effect similar to that of FM. Given the adverse effects of nonselective COX inhibitors, clinical application of MX may be beneficial in horses with SIRS/endotoxemia.
Topics: Animals; Horses; Meloxicam; Lipopolysaccharides; Endotoxemia; Anti-Inflammatory Agents, Non-Steroidal; Pain; Administration, Oral; Horse Diseases
PubMed: 36586521
DOI: 10.1016/j.jevs.2022.104205 -
Journal of Controlled Release :... Feb 2022For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a...
For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively. PCL allowed for sustained release of meloxicam over two weeks and was used as a carrier of meloxicam. Solid-state and image analyses indicated that the PCL matrices encapsulated meloxicam in crystalline clusters, which dissolved in aqueous medium and generated pores for subsequent drug release. The subcutaneously implanted meloxicam-loaded PCL matrices in rats showed pharmacokinetic profiles consistent with their in vitro release kinetics, where higher drug loading led to faster drug release. This study finds that the choice of polymer platform is crucial to continuous release of meloxicam and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices.
Topics: Animals; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Meloxicam; Polymers; Rats
PubMed: 34990702
DOI: 10.1016/j.jconrel.2021.12.038 -
Journal of Veterinary Pharmacology and... Jan 2020Use of drug in lactating animal should be carefully considered due to its possibility of changes in pharmacokinetics as well as drug penetration in milk. The aim of this...
Use of drug in lactating animal should be carefully considered due to its possibility of changes in pharmacokinetics as well as drug penetration in milk. The aim of this study was to assess the effect of lactation on pharmacokinetics of meloxicam after IV and IM administrations in goats. A crossover design (2 × 2) was used for each lactating and nonlactating group of goats with a 3-week washout period. Meloxicam (0.5 mg/kg) was administered into the jugular vein and upper gluteal muscle by IV and IM routes, respectively. The plasma and milk drug concentrations were determined by high-performance liquid chromatography with diode array detector, and the pharmacokinetic analysis was carried out by noncompartmental analysis. The pharmacokinetic parameters of meloxicam in lactating and nonlactating goats were not significantly different. The IM bioavailability of meloxicam was relatively lower in lactating (75.3 ± 18.6%) than nonlactating goats (103.8 ± 34.7%); however, the difference was not statistically significant. Moreover, AUC ratio between milk and plasma, which represent drug milk penetration, for both IV and IM administrations was less than 1 (about 0.3). In conclusion, pharmacokinetic parameters of meloxicam are not significantly altered by lactation for either the IV or IM routes of administration and this drug does not require a different dosage regimen for lactating animals.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Drug Residues; Female; Goats; Half-Life; Lactation; Meloxicam; Milk
PubMed: 31774176
DOI: 10.1111/jvp.12827 -
Fundamental & Clinical Pharmacology Jun 2022Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their...
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their applicability in analgesia if their ceiling and adverse effects are reduced. The aim of this study was to evaluate the pharmacological interaction of two NSAIDs, paracetamol and meloxicam, with the antipsychotic drug risperidone in mice, in several experimental tests of nociceptive and inflammatory pain. Antinociception was assessed by dose-response curves to paracetamol and meloxicam before and after the i.p. administration of 0.5 mg/kg of risperidone. Results are presented as means ± SEM and differences were calculated by one-way ANOVA followed by Tukey's post-test. Paracetamol and meloxicam produced a dose-related antinociceptive effect with diverse potencies. Risperidone increased the analgesia mediated by paracetamol and meloxicam only in the tonic tests that detected inflammatory pain. This suggests that COX inhibition is only a partial explanation of the increased analgesic potency of paracetamol and meloxicam since the effects of NSAIDs in the CNS are mediated by multiple mechanisms. These results indicate that the combination of risperidone with paracetamol or meloxicam could be a new and effective alternative for the management of inflammatory pain.
Topics: Acetaminophen; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Mice; Pain; Risperidone
PubMed: 34989439
DOI: 10.1111/fcp.12754 -
Neurochemical Research Aug 2020Epilepsy comes after stroke as the most common chronic neurological disorder worldwide. Inflammation enhances neuronal hyperexcitability that could provide a background...
Epilepsy comes after stroke as the most common chronic neurological disorder worldwide. Inflammation enhances neuronal hyperexcitability that could provide a background setting for the development of epilepsy. The aim of this study was to assess the effect of valproate (VAL), diclofenac (DIC), meloxicam (MEL), VAL + MEL and VAL + DIC in pentylenetetrazol (PTZ) kindled mice. Seventy mice were randomly allocated into 7 equal groups; Control, PTZ, VAL, DIC, MEL, VAL + MEL and VAL + DIC groups. Kindling was induced by PTZ (40 mg/kg, i.p.) injection every other day for 17 days. The drugs were administered, 30 min before each PTZ injection till the end of the schedule. Seizure score, latency, duration and mortality rate were recorded in all groups. Tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA) and prostaglandin E2 (PGE2) levels as well as reduced glutathione (GSH) content were assessed in brain homogenate at the end of the schedule. VAL, DIC, MEL, VAL + MEL and VAL + DIC decreased seizure score and duration. Meanwhile, they increased the latency period. PTZ increased TNF-α, IL-1β, MDA, and PGE2 levels meanwhile, it decreased GSH content. Administration of VAL, DIC, MEL, VAL + MEL and VAL + DIC decreased TNF-α, IL-1β, MDA, and PGE2 levels meanwhile, they increased GSH content in the brain homogenates. Effects of VAL + DIC combination on the studied parameters were significant in relation to VAL. VAL, DIC, MEL, VAL + MEL and VAL + DIC produced anticonvulsant effect and mitigated inflammation and oxidative stress in PTZ-kindled mice. Interestingly, DIC rather than MEL enhanced the anticonvulsant effect VAL.
Topics: Animals; Anticonvulsants; Diclofenac; Epilepsy; Kindling, Neurologic; Male; Meloxicam; Mice; Pentylenetetrazole; Seizures; Valproic Acid
PubMed: 32405761
DOI: 10.1007/s11064-020-03054-7 -
Contact Dermatitis Jul 2019Non-steroidal anti-inflammatory drugs constitute a main cause of fixed drug eruption (FDE). A few cases of piroxicam-induced FDE have been reported; however, the...
BACKGROUND
Non-steroidal anti-inflammatory drugs constitute a main cause of fixed drug eruption (FDE). A few cases of piroxicam-induced FDE have been reported; however, the cross-reactivity among oxicams has rarely been evaluated.
OBJECTIVES
To describe a series of patients with piroxicam-induced FDE, mostly confirmed by a positive patch test reaction, in whom cross-reactivity to meloxicam was assessed.
METHODS
We included all cases of piroxicam-induced FDE diagnosed in the department of pharmacovigilance of Monastir. Patch tests for piroxicam and meloxicam were performed in the involved skin according to the European Network on Drug Allergy recommendations. Oral provocation tests (OPTs) were performed for patients with negative skin test results.
RESULTS
Seven patients were included in this study. FDE was multiple for five patients and solitary for two. Bullous eruption was noticed in two cases. Lesional patch tests for piroxicam gave positive results in six patients. To assess cross-reactivity with meloxicam, this was patch tested. The test gave a positive result in only one patient. OPTs with meloxicam gave positive results in two patients with negative patch test results.
CONCLUSION
Meloxicam is not a safe alternative for the treatment of piroxicam-induced FDE, and OPTs can be used to confirm tolerance before this drug is prescribed as a safer alternative.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross Reactions; Drug Eruptions; Female; Humans; Male; Meloxicam; Middle Aged; Patch Tests; Piroxicam; Retrospective Studies
PubMed: 30663057
DOI: 10.1111/cod.13225 -
PloS One 2022The study aimed to fabricate and evaluate Meloxicam (MLX) loaded Hydroxypropyl Methylcellulose (HPMC) microparticles for colon targeting because MLX is a potent...
The study aimed to fabricate and evaluate Meloxicam (MLX) loaded Hydroxypropyl Methylcellulose (HPMC) microparticles for colon targeting because MLX is a potent analgesic used in the treatment of pain and inflammation associated with colorectal cancer (CRC). Nevertheless, its efficiency is limited by poor solubility and gastrointestinal tracts (GIT) associated side effects. Seventeen formulations of MLX loaded HPMC microparticles were fabricated by the oil-in-oil (O/O)/ emulsion solvent evaporation (ESE) technique. A 3-factor, 3-level Box Behnken (BBD) statistical design was used to estimate the combined effects of the independent variables on the dependent variables (responses), such as the percent yield (R1), the entrapment efficiency (EE) (R2), mean particle size (R3) and in vitro percentage of cumulative drug release (R4). For physicochemical characterization FTIR, XRD, DSC, and SEM analyses were performed. Biocompatibility and non-toxicity were confirmed by in-vivo acute oral toxicity determination. The percentage yield and EE were 65.75-90.71%, and 70.62-88.37%, respectively. However, the mean particle size was 62.89-284.55 μm, and the in vitro cumulative drug release percentage was 74.25-92.64% for 24 hours. FTIR analysis showed that the composition of the particles was completely compatible, while XRD analysis confirmed the crystalline nature of the pure drug and its transition into an amorphous state after formulation. DSC analysis revealed the thermal stability of the formulations. The SEM analysis showed dense spherical particles. The toxicity study in albino rabbits showed no toxicity and was found biocompatible. The histopathological evaluation showed no signs of altered patterns. Results of this study highlighted a standard colonic drug delivery system with the ability to improve patient adherence and reduce GIT drug-associated side effects in CRC treatment.
Topics: Animals; Colon; Drug Delivery Systems; Humans; Hypromellose Derivatives; Meloxicam; Rabbits; Solubility
PubMed: 35468155
DOI: 10.1371/journal.pone.0267306 -
Biochemical Pharmacology May 2020ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the...
ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the pharmacokinetics, brain accumulation and secretion into milk of several compounds, including antitumoral, antimicrobial and anti-inflammatory drugs. The aim of this study was to investigate whether the widely used anti-inflammatory drug meloxicam is an Abcg2 sustrate, and how this transporter affects its systemic distribution. Using polarized ABCG2-transduced cell lines, we found that meloxicam is efficiently transported by murine Abcg2 and human ABCG2. After oral administration of meloxicam, the area under the plasma concentration-time curve in Abcg2 mice was 2-fold higher than in wild type mice (146.06 ± 10.57 µg·h/ml versus 73.80 ± 10.00 µg·h/ml). Differences in meloxicam distribution were reported for several tissues after oral and intravenous administration, with a 20-fold higher concentration in the brain of Abcg2 after oral administration. Meloxicam secretion into milk was also affected by the transporter, with a 2-fold higher milk-to-plasma ratio in wild-type compared with Abcg2 lactating female mice after oral and intravenous administration. We conclude that Abcg2 is an important determinant of the plasma and brain distribution of meloxicam and is clearly involved in its secretion into milk.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Administration, Intravenous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dogs; Female; Humans; Madin Darby Canine Kidney Cells; Male; Meloxicam; Mice; Mice, Knockout; Milk; Tissue Distribution
PubMed: 32217099
DOI: 10.1016/j.bcp.2020.113924